Managing Fresh-Frozen Plasma Transfusion Adverse Effects: Allergic Reactions, TACO, and TRALI

What is Managing Fresh-Frozen Plasma Transfusion Adverse Effects: Allergic Reactions, TACO, and TRALI?

Transfusing fresh-frozen plasma, a key part of modern medicine, is often used to manage blood clotting disorders and help patients who are in need. However, like any medical procedure, it carries potential risks that doctors need to be prepared to handle. Specifically, we see three main types of adverse effects: allergic reactions, fluid overload in the circulatory system, and acute lung injury related to transfusion. Though these complications may vary in how they present and their underlying causes, they highlight the need for doctors to have a thorough understanding and to be extremely watchful when giving fresh-frozen plasma. This helps ensure that it works as intended while also keeping the patients safe.

Blood contains elements like plasma, red blood cells, platelets, and white blood cells, which circulate throughout our bodies. Doctors separate these components in a device known as a refrigerated centrifuge, which spins the blood at a high speed. This separates the components due to their differing properties. Whole blood is subjected to a hard spin, and as a result, the red blood cells settle at the bottom, with white cells above them and the platelets on top. A milder spin is used to get plasma that is rich in platelets. We can also separate these components using a method known as apheresis, which allows us to collect specific components from a donor’s blood. The collected blood is stored in special bags with a solution called CPDA to keep the blood from clotting.

Fresh-frozen plasma is a part of the blood that has been separated and frozen within 8 hours to keep the clotting factors preserved. The idea of using plasma as a blood substitute was first suggested by Dr. John Elliott in 1936 and later developed by Dr. Max Strumia for military use during World War II. After the war, plasma transfusion started being used more often in medicine. With time, stronger measures have been put in place to screen for diseases and improve safety, thus reducing complications related to plasma transfusion.

Fresh-frozen plasma can be stored at extremely low temperatures (-25°C or below) for up to 36 months. This plasma contains stable and labile (fragile) coagulation factors, plasma proteins, fibrinogen, and factor VIII. The low temperatures help preserve these delicate factors. The plasma is thawed in a warm water bath at 37°C and should be used quickly once thawed. If immediate use is not possible, the plasma should be stored and used within either 4 hours at 22±2°C or 120 hours at 4±2°C.

Plasma transfusion is often recommended for individuals with single or multiple clotting factor deficiencies, a condition called acute disseminated intravascular coagulation, a need for immediate reversal of warfarin’s effects, a condition called thrombotic thrombocytopenic purpura, or in cases of massive transfusions. Other indications include liver diseases, certain paediatric conditions, and surgeries that involve the heart and lungs. Transfusion reactions can range from minor to severe, and they may occur immediately or be delayed. Such reactions could be due to immune responses or other factors. Some examples of acute reactions are acute hemolytic reactions, allergic reactions, anaphylactic reactions, bacterial contamination and lung injury or fluid overload related to transfusion. Delayed reactions may include delayed hemolysis (breakdown of red blood cells), transmission of infections, and a condition called post-transfusion purpura. If a reaction is suspected, the transfusion must be stopped immediately and the blood bank and doctor must be informed.

What Causes Managing Fresh-Frozen Plasma Transfusion Adverse Effects: Allergic Reactions, TACO, and TRALI?

Adverse reactions associated with a transfusion can happen immediately or within 24 hours of transfusion, and can be caused by the immune system reacting to the transfusion, or for non-immune related reasons. These reactions can be due to several different factors.

The plasma in blood transfusions may cause reactions because of certain antibodies in the blood known as human leukocyte antigen (anti-HLA) and human neutrophil antigen (anti-HNA). Usually, it’s the class II HLA antibodies related more frequently.

Allergic reactions can occur when the body’s antibodies react to allergens from the donor blood. Detecting the specific proteins that cause these reactions can be difficult. Often, human immunoglobulin (IgA) and haptoglobin can provoke these reactions, especially in individuals deficient in IgA. Other substances, like methylene blue-treated plasma, can also be linked to these allergic reactions.

Febrile nonhemolytic transfusion reactions (FNHTR) – reactions that cause a fever but not the breakage of red blood cells – are rare with plasma transfusions as the plasma is usually devoid of cells. However, if white blood cells have contaminated the transfused plasma and survived the freezing and thawing process, FNHTR can occur. Acute hemolytic transfusion reactions (AHTR), where red blood cells break down, can commonly happen if the plasma transfused is not compatible with the patient’s blood type. Pieces of red blood cells remaining in the plasma can also trigger AHTR.

TRALI, a reaction that causes lung damage, is believed to be due to two “hits”. The first “hit” involves the patient’s pre-existing health condition that primes certain white blood cells (neutrophils) in the lung. The second “hit” comes from the transfusion which triggers these neutrophils, leading to lung damage. Donor plasma that contains specific antibodies – HLA and HNA – can cause TRALI, especially if the plasma came from a female donor who has been pregnant before.

Transfusion Associated Circulatory Overload or TACO, a reaction that can cause fluid to accumulate in the lungs, can be attributed to several risk factors including heart failure, kidney failure, excess fluid, old age, and poor fluid management. Certain proteins called cytokines (IL-8 and IL-10) may play a role in TACO. The exact process causing this fluid build-up is still being researched.

Reactions not related to the immune system can be caused by bacterial contamination, excess fluid (circular overload), and certain chemical reactions such as excessive citrates. While the risk of infection from plasma transfusion is low due to extensive screening, infections like HIV, hepatitis B and C can still occur. Bacteria can be introduced during the thawing process, with organisms like Staphylococcus, Klebsiella, Propionibacterium, and Pseudomonas being potential culprits.

Delayed transfusion reactions, which can happen between 24 hours and 30 days, are usually due to a memory response from the immune system to foreign substances it has encountered before. These reactions can cause the destruction of red blood cells or even a rare condition called transfusion-associated graft-versus-host disease (TA-GVHD), which is unlikely because thawed plasma rarely contains the viable lymphocytes that are needed for TA-GVHD to develop.

Risk Factors and Frequency for Managing Fresh-Frozen Plasma Transfusion Adverse Effects: Allergic Reactions, TACO, and TRALI

In the US, for every 100,000 blood transfusions given, there are about 282 reported instances of reactions. These reactions can vary widely when it comes to the transfusion of fresh-frozen plasma. On average, the number of reactions for each type of transfusion issue is:

• Allergic reactions occur 92 times for every 100,000 units transfused.
• Anaphylactic reactions happen about 0.8 times for every 100,000 units transfused.
• Febrile nonhemolytic transfusion reactions (FNHTRs) occur 12 times for every 100,000 units transfused.
• Transfusion-associated circulatory overload (TACO) happens 6 times for every 100,000 units transfused.
• Transfusion-related acute lung injury (TRALI) occurs 1.8 times for every 100,000 units transfused.

After a transfusion, the risk of a Hepatitis B (HBV) infection is somewhere between 1 in 357,000 to 1 in 280,000 per transfusion. The risk of HIV and Hepatitis C (HCV) infections are even lower – around 1 in 1,467,000 and 1 in 1,149,000, respectively.

Signs and Symptoms of Managing Fresh-Frozen Plasma Transfusion Adverse Effects: Allergic Reactions, TACO, and TRALI

Starting a transfusion requires a complete medical history and check of the patient’s vital signs. Doctors need to know about any medical conditions such as IgA deficiency, haptoglobin deficiency, heart or kidney issues, any past transfusions, and the patient’s family and social history. The patient and the details on the blood bag need to be verified before the transfusion begins. Vital signs need to be monitored every 15 minutes or monitored continuously. Doctors also look out for signs of complications like a fever, chills, skin reactions, swelling, low blood pressure, and difficulty breathing. Small changes in vital signs are normal. In patients who have experienced trauma or are critically ill, the transfusion rate must be closely monitored. Doctors also stay alert for symptoms of lung injury (TRALI) and overload (TACO), as these conditions need to be detected and treated early to ensure the patient stays safe during the transfusion.

Allergic reactions during transfusions can result in skin reactions, itchiness, and flushed skin. Anaphylactic reactions are more serious and can cause difficulty breathing, wheezing, swelling, chest tightness, nausea, vomiting, increased heart rate, low blood pressure, and shock. In FNHTR, the patient may get fevers and chills.

Symptoms of hemolytic transfusion (destruction of red blood cells) include fever, abdominal pain, red or brown urine, chills, low blood pressure, and back pain. Severe cases can lead to kidney failure or abnormal blood clotting. This is a significant complication and needs to be treated immediately.

TRALI and TACO both feature sudden onset of difficulty breathing within six hours of a transfusion. They can also present with bilateral infiltrates, signs of fluid buildup in the lungs visible on an x-ray, low blood oxygen levels, and low blood pressure. Both conditions require immediate attention.

There are two types of TRALI, differentiated by risk factors for, and diagnosis of, Acute Respiratory Distress Syndrome (ARDS).

• TRALI Type I occurs in patients without risk factors for ARDS, presenting with:
• Sudden hypoxemia (low blood oxygen), visible on an x-ray
• Pulmonary edema (fluid buildup in lungs)
• The absence of left atrial hypertension (no high blood pressure from the heart to the lungs)
• Symptoms within six hours of transfusion
• No other risk factors for ARDS
• TRALI Type II happens in at-risk patients, or those with mild ARDS, but show worsening of symptoms with transfusion:
• Sudden hypoxemia and pulmonary edema in a patient with stable respiratory status before the transfusion

In cases of TACO, symptoms can be sudden breathing difficulties, puffy neck veins, abnormal lung sounds, heart sounds, high blood pressure, and fever.

• The clinical definition of TACO includes:
• New or worse symptoms within six hours of transfusion
• Breathing difficulties such as shortness of breath, need to sit upright to breathe, and cough
• Evidence of fluid surplus
• Elevation in a heart-related hormone
• Evidence of fluid buildup in the lungs from the x-ray
• Evidence of heart failure
• Increased central vein pressure

Taking note of delayed reactions to transfusion is also essential. These can cause fever, yellowing of the skin and eyes (jaundice), and a drop in hemoglobin concentration 2 to 4 weeks after the transfusion. A condition called Posttransfusion purpura can cause severe bleeding from various areas due to a steep drop in blood platelets within two weeks of transfusion. Other symptoms include fever, chills, and resistance to platelet transfusion.

Testing for Managing Fresh-Frozen Plasma Transfusion Adverse Effects: Allergic Reactions, TACO, and TRALI

Recognizing the signs and symptoms is a vital step in treating reactions from blood transfusions. The first step is to assess how severe the reaction is. Symptoms may include fever, chills, an itchy rash (also known as urticaria), difficulty breathing, or low blood pressure. Mild reactions may only cause small changes in vital signs or minor symptoms. This can include a small fever increase—about 1 to 2 degrees Celsius from normal—and temporary hives without other major symptoms or significant bodily changes.

If a reaction occurs, the transfusion has to be stopped straight away. Any protocols in place for dealing with a transfusion reaction should be activated. The blood bank must be informed immediately. It’s critical to check the label on the plasma component and all related records for any potential mistakes. The unit of blood needs to be examined for discoloration and clumps. It’s important to keep the vein open for access. The patient’s airway, breathing, and circulation should be assessed. The patient should be checked for low blood pressure and shock, severe respiratory distress, signs of infection, severe shivering or pain, fever, rash, or hives. Once the patient has been stabilized initially, additional evaluations may be required, and a decision about whether to continue or stop the transfusion needs to be taken.

Examinations are performed on the plasma transfusions before and after the reaction to see if there’s any hemolysis (breakdown of red blood cells) or jaundice (yellowing of the skin or eyes). Blood samples are taken for cultures if an infection is suspected. For allergic and anaphylactic reactions, basophil activation test (BAT, a test to see if your immune system is working properly) and tryptase levels (a sign of an allergic reaction) may be checked. If a deficiency of IgA or Haptoglobin is suspected, these can also be tested. In the case of acute hemolytic transfusion reaction (AHTR, a serious complication of blood transfusions), other tests such as peripheral smear, bilirubin, haptoglobin, lactate dehydrogenase, coombs test, and total counts can be evaluated.

When dealing with transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO), a chest X-ray, B-type natriuretic peptide (BNP), and NT-proBNP can be obtained. It is crucial to confirm whether the patient is experiencing a circulatory overload (too much fluid in the body). Total blood counts can be used to check for delayed hemolytic transfusion reactions (DHTR, a rare complication of a blood transfusion) and post-transfusion purpura (a complication that can occur after a blood transfusion, causing a low platelet count).

Treatment Options for Managing Fresh-Frozen Plasma Transfusion Adverse Effects: Allergic Reactions, TACO, and TRALI

After a doctor assesses a patient’s symptoms, they begin treatment to alleviate these symptoms. If the patient has low blood pressure (hypotension) and is in shock, the doctor will provide fluids and medications (vasopressors) to raise the blood pressure. If the patient is experiencing severe breathing difficulties, various treatments, including oxygen, adrenaline (epinephrine), antihistamines, and corticosteroids, are used. In situations where there are signs of too much fluid in the body (volume overload), the doctor will administer drugs to help eliminate excess fluids (IV diuretics) and oxygen. If there is an indication of infection (sepsis), the doctor will take blood samples for testing (cultures) and provide a wide range of antibiotics (broad-spectrum antibiotics). Fever is treated with medication (antipyretics), and hives or rash are treated with antihistamines.

Allergic reactions to blood transfusions are treated according to their severity. For minor reactions, antihistamines are used. If these treatments improve the patient’s symptoms, the blood transfusion may be able to continue under careful monitoring. However, if symptoms continue, the transfusion must be stopped. In cases of severe allergic reactions or anaphylaxis, the medical team will check the patient’s airway, breathing, and circulation, and provide adrenaline, oxygen, IV fluids, and certain medications (methylprednisolone or prednisolone, and antihistamines). Medications (bronchodilators or β2-agonists) are used for bronchospasms, which are spasms in the lung’s small air passages. In rare instances, patients with a specific immune deficiency (IgA) will need blood from similar IgA-deficient donors.

Transient FNHTRs are treated with simple pain relievers like paracetamol/acetaminophen or NSAIDs. If an infection is suspected to have been transmitted through the transfusion, blood tests are done, and broad-spectrum antibiotics are started. The reaction due to incompatible blood plasma (AHTR) can be avoided by using compatible plasma.

If a lung injury associated with a transfusion (TRALI) is suspected, the transfusion is immediately stopped. The patient’s airway and breathing are assessed, and if necessary, a ventilator will be used. The physician will also check for fluid overload, and an X-ray image of the chest will be taken. The treatment mainly involves supportive care. There are several experimental treatments being researched including IL-10 therapy, blocking IL-8 receptors, and reducing C-reactive protein (CRP) levels.

In the case of TACO, which is a form of lung injury triggered by a blood transfusion, raising the head-end of the bed, administering oxygen, and giving diuretics usually lead to a rapid improvement. Noninvasive ventilation might help improve breathing. Proper fluid management and treatment of any underlying conditions are essential. In case of worsening respiratory symptoms, intubation and mechanical ventilation may be needed, using a lung-protective ventilation strategy.

Please refer to the table titled ‘FFP Reactions’ for a complete list of signs, symptoms, and methods of managing reactions to fresh-frozen plasma transfusions.

What else can Managing Fresh-Frozen Plasma Transfusion Adverse Effects: Allergic Reactions, TACO, and TRALI be?

When dealing with different types of reaction after a transfusion, doctors may consider various underlying conditions that might cause the symptoms. These could include:

• Acute Respiratory Distress Syndrome (ARDS)
• Anaphylaxis (Severe allergic reaction)
• Disseminated Intravascular Coagulation (Blood clotting disorder)
• Septicemia (Blood infection)
• Cardiogenic Pulmonary Edema (Fluid build-up caused by heart issues)
• Infections

It might be challenging to differentiate between Transfusion Related Acute Lung Injury (TRALI) and Transfusion Associated Circulatory Overload (TACO) as both have similar symptoms, which are also similar to those of ARDS. All these conditions cause breathing issues and similar images on chest x-rays.

Doctors use an ultrasound of the heart (echocardiography) to understand the volume status and diastolic dysfunction. They also look at the pressure in the pulmonary artery and protein levels in the lung fluid. However, these findings may not give clear results. To confirm a diagnosis of TACO, they also look at levels of a specific hormone in the blood (B-type natriuretic peptide or BNP) and N-terminal pro-B type natriuretic peptide (NT-proBNP) and use these results together with the patient’s symptoms.

What to expect with Managing Fresh-Frozen Plasma Transfusion Adverse Effects: Allergic Reactions, TACO, and TRALI

Plasma transfusions can typically be carried out safely, and most patients experience good outcomes after having allergic, febrile nonhemolytic, or hemolytic reactions to the transfusion. However, trauma patients receiving fresh-frozen plasma transfusions might be at a higher risk of developing additional health problems, like ARDS (Acute Respiratory Distress Syndrome) or failure of multiple organs, after their initial injuries. It is also important to note that critically ill patients may face higher risks of complications from fresh-frozen plasma transfusions.

In the case of patients with TRALI (Transfusion Related Acute Lung Injury), the prognosis is usually positive. Their condition often improves within 3 to 4 days after the initial incident. Pulmonary infiltrates, which are a collection of substances like fluid or cells that enter the lungs and can lead to other problems, typically go away relatively quickly. However, in some cases, these infiltrates can linger for more than a week, showing that recovery times can vary among TRALI patients.

Possible Complications When Diagnosed with Managing Fresh-Frozen Plasma Transfusion Adverse Effects: Allergic Reactions, TACO, and TRALI

Transfusing plasma into a patient may cause different complications. These could range from mild allergic reactions to severe and potentially fatal conditions like TACO (Transfusion-Associated Circulatory Overload) and TRALI (Transfusion-Related Acute Lung Injury). When a patient has an allergic reaction to the transfusion, even though it is typically not severe, it could require more tests and result in a longer hospital stay. On the contrary, FNHTRs (Febrile Non-Hemolytic Transfusion Reactions) usually improve quickly with the administration of treatments to reduce fever. The key to managing these complications is to recognize them early, and proper actions need to be executed promptly to guarantee the patient’s safety.

Both TACO and TRALI are grave concerns. TRALI could worsen a patient’s lung conditions and is mainly tackled through supportive care. The death rate associated with TRALI is usually between 5 to 10%, emphasizing the seriousness of this condition. TACO can be even more detrimental, with recorded death rates ranging from 14-29%, highlighting the potentially fatal nature of this condition.

Common issues with Plasma Transfusion:

• Mild allergic reactions
• TACO (Transfusion-Associated Circulatory Overload)
• TRALI (Transfusion-Related Acute Lung Injury)
• Risk of prolonged hospital stay due to additional testing
• FNHTRs (Febrile Non-Hemolytic Transfusion Reactions) that can be managed with fever-reducing treatments
• Potential worsening of patient’s lung condition (TRALI)
• Mortality rate of 5 to 10% with TRALI
• Mortality rate of 14 to 29% with TACO

Preventing Managing Fresh-Frozen Plasma Transfusion Adverse Effects: Allergic Reactions, TACO, and TRALI

Having a conversation with patients about the need for a plasma transfusion, which refers to the process of giving blood plasma through an injection, is very important. This conversation should cover why the transfusion is needed, what benefits it might offer and what the possible side effects are. Safety measures, including something called crossmatching – which is a test to make sure the patient’s blood and the donor’s blood are compatible – and careful monitoring are also part of the discussion.

Patients should also be told about the common symptoms that might indicate they’re having a reaction to the transfusion, and urged to report any unusual feelings they have right away. It’s also crucial to give patients the chance to ask questions and seek further information, to make sure they understand the procedure fully and feel comfortable making decisions about their treatment.